ABSTRACT The striking identification of select patients who were able to durably control HIV rebound after ART discontinuation in the ANRS Visconti cohort, or in cases such as the Mississippi baby, have highlighted the possibility of sustained HIV remission and provided the first proof of concept that HIV remission may be clinically achievable. In several of these cases, post-treatment control is characterized by the very low, but detectable presence of HIV infected cells implying that in at least some cases of viral remission, a balance may have been struck between HIV-1 and the host. The mechanism(s) by which these reservoirs are subject to sustained virologic remission or ultimately rebound, upon ART interruption is not understood. Moreover, there is no validated biomarker that can predict clinical outcome during a treatment interruption. Therefore, a detailed understanding of the factors that dictate HIV suppression or relapse, in the absence of antiretroviral therapy, is critical to develop approaches to therapeutically foster HIV-1 remission in ART-treated patients. Thus, we propose detailed studies to define the impact of early antiretroviral therapy on virologic and immunologic outcomes that are relevant to achieving HIV remission and durable virus control after the cessation of ART. These studies encompass multi-disciplinary collaborations, to have the greatest breadth of investigation, and ultimately the greatest scientific impact. Our proposed investigations include analytic studies in both HIV-infected adult and pediatric patients. We will also conduct parallel studies in non- human primates, including the pre-clinical evaluation of novel eradication therapeutics.